Portable digital diagnostic device

ABSTRACT

A computerized device provides microscopy and electrochemistry tests, performed in dual channels. The device can be brought to the field, for on-site testing with instant results. The dual channels include an imaging channel and a signal channel.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is related to and claims priority from commonly ownedU.S. Provisional Patent Application Ser. No. 62/454,933, entitled:Portable Digital Diagnostic Device, filed on Feb. 6, 2017, thedisclosure of which is incorporated by reference in its entirety herein.

TECHNICAL FIELD

The present invention is directed to portable apparatus for onsitedisease diagnosis.

BACKGROUND

Numerous clinical tests require a blood sample to be taken in order toprovide a diagnosis. Presently, the patient must give a blood sample,either on or off site, and then wait for test results, as the bloodsample must be taken to a laboratory for analysis, typically bymicroscopy, performed by trained personnel. Even getting the bloodsample must be done by trained personnel, using syringes, butterflyneedles, blood tubes and other blood collection devices. The bloodcollection devices must be stored properly and maintained in a sanitarymanner, so as not to become contaminated and thus, cannot be used. Also,once the blood sample reaches the microscopist, it must be properly“smeared”, in order to be usable for microscopy or other analysis.

Microscopy is the “gold standard” for laboratory analysis. In more than50% of the world, clinics with microscopic equipment are rare, as wellas trained microscopists to prepare operate the microscopy equipment andprovide a diagnosis of the blood or tissue sample. Moreover, obtaining atest result from microscopy takes time, and is certainly notinstantaneous, even if the microscopy lag and microscopist are on site,at a medical clinic, hospital, or the like. Also, in many parts of theworld, trained microscopists and laboratories with suitable microscopicequipment for the microscopist are limited, and may be far away fromvarious populations, such as rural populations, adding additionaldifficulty to getting a blood test with a result determined bymicroscopy.

There are also problems associated with transporting a blood sample to amicroscopy laboratory, due to possible improper handling of the sample,as well as possible spoliation of the sample, due to weather and time intransit, from the patient to the laboratory. Such blood tests are alsoexpensive to many people in the world, eliminating many people fromgetting such tests. Moreover, as the result is not instant, andtypically off site, patients may not be able to be charted forstatistical studies, and infected patients who require immediatetreatment may not be able to be located quickly.

Rapid Diagnostic Tests (RDTs) provide instant results. However, thereare not RDTs for many diseases and the detection of disease is withoutsignificant sensitivity which is needed for early detection andtypically has poor specificity. These RDT devices must be properlystored and handles, so as to maintain accuracy and reliability. Also,there are many manufactures of RDTs and quality of the RDTs variesgreatly between manufacturers.

As diseases spread rapidly, it is important to diagnose them quickly andin the early stages. This ensures that patients can be treated quickly,so as to maintain their health, as well as prevent the disease fromspreading. In many locations all over the world, this is simply notpossible, due to the lack of laboratory facilities, coupled with thelack of trained experts who can properly identify diseases.

Also, for some diseases, such as malaria, additional tests are needed,such as a Glucose-6-phosphate Dehydrogenase (G6PD) deficiency test—inorder to decide on the safest and proper treatment (based on WHOguidelines for malaria elimination and eradication). This test, inaddition to the malaria diagnostics, is typically not available and notaccessible in many rural and remote locations areas of the world.

SUMMARY

The present invention provides a computerized device which bringsmicroscopy and electrochemistry tests to the field, for on-site testingwith instant results, for example, in real time with minimally trainedoperator that can be a community-health-work and not only physician Thecomputerized device is a single hand held device, which can be broughtto remote areas, giving millions of people access to healthcare thatthey did not have previously. Since instant results are obtained, theunnecessary use of drugs, such as un-necessary antibiotic and/orantimalarial is eliminated, as diseases and conditions are provided withcertainty, on the spot. Additionally, since disease and conditions aredetected instantly, treatment protocols can begin immediately,eliminating the spread of infectious and deadly diseases and conditions.

The computerized device is a dual channel device, one channel forimaging or microscopy, and one channel for electrochemistry (signals).Based on results from these two channels, a diagnosis can be made thatis more accurate and effective than is presently possible in the field.This allows for rapid and safe treatment and follow-up of disease,inhibiting its spreading, as well as allowing for real-time mappingpatients, in order to track movement of diseases in real-time and obtainother data for immediate and effective intervention of healthauthorities, studies, and the like. The device is, for example, alab-on-hand computerized platform, which is programmable for variousmedical diagnostic applications based on the same RevDx hardwareplatform

The disclosed device allows for receiving a blood sample, that can betaken by the user or medical personnel with little or any training, witha finger prick, and does not need trained medical personnel. Thedisclosed device, is designed to be coupled to a mobile device or mobilecomputer, such as a smart phone, with the device designed for analyzingthe blood sample, and provide an instant diagnosis on site and in realtime. As the device performs its analysis by techniques such as machinelearning, and other network connectivity, such as telemedicine, wherethe image of the blood sample, is transmitted over a network, such asthe internet, to trained medical personnel, in remote locations.

By obtaining this sensitive and accurate diagnosis instantly, thepatient can be treated much sooner that would be done conventionally.This preserves the health of the patient, and where the disease iscontagious, prevents that disease from spreading.

The present invention uses disposable sample preparation kit based onmicrofluidic technologies and or biosensor/electrochemistry strips, withcorresponding reading and analysis systems to diagnose different or dualaspects of diseases, typically on site. For example, with Malaria, themicrofluidic chips, accompanied by their reading and analysis, are ableto detect the malaria parasite type with a high sensitivity andspecificity, allowing for detection of malaria in early stages, whereparasite density is low (when compared to advanced stages of Malaria).The biosensor strip and reader channel is used to detect G6PDdeficiency. This is essential to ensure that treatment with the drugprimaquine used for the malaria parasite Plasmodium vivax isadministered safely. In addition, primaquine is used to preventtransmission of other malaria parasites types. The biosensor readerchannel will also be used for glucose level monitoring. As malaria cancause hypoglycemia (dangerously low level of glucose), this will aid indeciding which patients need admission to a hospital.

Moreover, as the microfluidic chip and biosensor strip are bothdisposable and receive a blood sample at the time of testing, theprocess is sanitary, as disease does not pass between patients beingtested, accurate, as there is no chance of blood spoliation, and manypatients can be tested in a small amount of time by minimally trained oruntrained medical personnel. Additionally, the micro fluidic chips andbiosensor strips require small amounts of blood, usable as blood smears.The blood is obtained, for example, by a finger prick, which can beperformed by the user or someone without medical training or withminimal medical training.

Also, the process is inexpensive, as the microfluidic chips andbiosensor strips are inexpensive, with the device used being a one-timepurchase, capable of multiple uses.

Embodiments of the present invention are directed to a device foranalyzing disease conditions. The device comprises: an imaging channelconfigured for providing a viewable sample; and, a signal channelincluding a signal analyzer for analyzing received signals based onelectrochemical responses emitted from an electrode having reacted to asample, to determine the existence of the disease condition.

Optionally, the device additionally comprises: an analytics moduleconfigured for scanning an image of the viewable sample, and determiningthe existence of the disease condition from the scanned image.

Optionally, the analytics module is configured for determining, from thescanned image, the existence of a disease condition selected from thegroup consisting of: G6PD deficiency output, blood glucose levels,malaria parasites including, P. falciparum, P. vivax, P. malaria. P.ovale, P. knowlesi and the disease stage, complete blood cell counts,multi-parasites including relapsing fever and Filarias, Tuberculosis,Pap smear analysis, urine tests and/or analysis and veterinary diseases

Optionally, the device additionally comprises: an optomechanical systemfor magnifying and scanning the sample, the optomechanical system incommunication with the analytics module.

Optionally, the device additionally comprises: a processor programmed todetermine a treatment for the disease condition, the processor incommunication with the analytics module.

Optionally, the device additionally comprises: a processor programmed todetermine a treatment for the disease condition, the processor incommunication with the analytics module and the signal analyzer.

Optionally, the imaging channel and the signal channel are configured tooutput the determination of the existence of the disease condition inreal time.

Optionally, the device includes a display in communication with theimaging channel and the signal channel.

Optionally, the display includes one or more of: 1) a screen display,and, 2) a display output configured for communicating with an imagesensor of an external computer device for displaying graphics on thedisplay screen of the external computer device.

Optionally, the imaging channel includes a first end for receiving thesample, and an oppositely disposed second end associated with thedisplay.

Optionally, the device additionally comprises: an analog to digitalsignal converter (ADC) in communication with the signal analyzer; and, asignal reader for reading the electrochemical signals (e.g., analogsignals) emitted from the electrode having reacted to the sample, thesignal reader in communication with the ADC.

Optionally, the signal analyzer is configured for analyzing signalsdetermine disease conditions selected from the group consisting of: G6PDoutput, blood glucose levels, malaria parasites including: P.falciparum, P. vivax, P. malaria. P. ovale, and the disease stage,complete blood cell counts, multi-parasites including: relapsing feverand Filarias, Tuberculosis, Pap smear analysis, and veterinary diseases.

Optionally, the device additionally comprises: a processor programmed totransmit data to the display which causes presentation of a UserInterface (UI) graphic display of the presence the disease condition.

Optionally, the device additionally comprises: a location module incommunication with at least one of the imaging channel or the signalchannel, the location module configured for displaying real-timelocation indications based on Global Positioning System (GPS) mapping ofthe detection of the disease condition.

Optionally, the device additionally comprises: a first port forreceiving a microfluidic chip holding the sample for being renderedviewable in the imaging channel; and, a second port for receiving anelectrode holding the sample in the signal channel.

Optionally, the device additionally comprises: a microfluidic chip forsample preparation for receipt in the first port.

Optionally, the device additionally comprises: a biosensor stripincluding an electrode for producing an electrochemical response whencontacted by a sample, for receipt in the second port.

Optionally, the sample includes portions of the same sample and thesample includes at least one of blood, urine, and tissue.

Optionally, the microfluidic chip is configured for mixing the sample,with one or more of staining agents, imaging enhancers, and dilatants.

Embodiments of the invention are directed to a method for analyzing, forexample, automatically analyzing, disease conditions. The methodcomprises: providing a sample to an imaging channel of a deviceincluding a display for viewing on the display; and, providing a sampleto a signal channel of the device, the device including a signalanalyzer, and the signal analyzer analyzing received signals based onelectrochemical responses emitted from an electrode having reacted tothe sample, to determine the existence of the disease condition.

Optionally, the method is such that information as to the diseasecondition detected by signal analyzer is displayable on the display.

Optionally, the method is such that the sample provided to the imagingchannel and the sample provided to the signal channel include portionsof the same sample and the sample includes at least one of blood, urine,and tissue.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings, where likereference numerals or characters represent corresponding or likeelements. With specific reference now to the drawings in detail, it isstressed that the particulars shown are by way of example and forpurposes of illustrative discussion of embodiments of the invention. Inthis regard, the description taken with the drawings makes apparent tothose skilled in the art how embodiments of the invention may bepracticed.

Attention is now directed to the drawing figures where like referencenumerals or characters refer to corresponding or like components. Thedrawing figures are as follows.

FIG. 1 is a diagram showing an exemplary environment in whichembodiments of the invention are performed;

FIG. 2 is a block diagram of the base and computer device as used incombination, also showing how these devices are linked to networks;

FIG. 3 is a schematic diagram of the base and computer device as used incombination;

FIG. 4A is a flow diagram for an exemplary process of the microscopyaspect of the present invention;

FIG. 4B is a flow diagram for an exemplary process of theelectrochemistry aspect of the present invention;

FIG. 5A is a block diagram of a standalone computer device in accordancewith embodiments of the invention;

FIG. 5B is a block diagram of another standalone computer device inaccordance with embodiments of the invention;

FIG. 5C is a perspective view of the device of FIG. 5B;

FIGS. 6A-6D are illustrations of microfluidic apparatus for thedisclosed devices;

FIG. 7 is a flow diagram of a process performed by the disclosed devicesfor determining malaria and if, detected, issuing a treatment protocol;and,

FIGS. 8A-8D are screen diagrams of the device of FIGS. 5B and 5C whilethe device is in operation.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example embodiment of the invention, where an electronicdevice 100, in the form of a base (the electronic device 100 also knownas a base, with these terms being used interchangeably herein), receivesa mobile computing device, for example, a smart phone 102, including adisplay screen 103, in a mechanical engagement, so as to be directlylinked to the optics and in electronic and/or data communication to eachother. The base 100 and smart phone 102 may also be linked to each otherthrough communications networks, such as a wide area or public networksuch as the Internet. There may also be linking via near fieldcommunications and other electronic communication formats and directlinks through an Input/Output (I/O) port of a communications module 254(FIG. 2 ).

The base 100 includes one port 110 for receiving a disposable samplepreparation chip/cassette based on microfluidic technologies 112, onwhich is, for example, a blood sample, for analysis, and another port114 for receiving a biosensor strip 116, which receives a blood sample,at an operative end 116 a, for example, on an electrode 116 b. The ports110, 114 are associated with channels. Port 110 serves as the inlet fora microscopy or imaging or microscopic channel (the terms “imagingchannel”, “microscopic channel” and “optic/optical channel” usedinterchangeably herein), for example, with malaria, identifying thespecific parasite (type of malaria) and the stage of malaria and alsofor Complete Blood Count (CBC) applications. The other port 114 servesas a signal channel or electrochemical channel (“signal channel” and“electrochemical channel” used interchangeably herein), for analyzingelectrochemical signals from the blood sample on the electrode 116 b ofthe biosensor strip 116, and for example, for malaria infected patients,determining whether there is a Glucose-6-Phosphate Dehydrogenase (G6PD)deficiency to decide on the appropriate and precise medication.

FIG. 2 shows a block diagram of the base 100 and the smart phone 102.The base 100 and smart phone 102 are shown directly connected to eachother, and are linked to one or more networks 200, such as local areanetworks (LANs), and wide area networks (WANs), including publicnetworks, such as the Internet, cellular networks and othercommunications networks.

Both channels, the imaging channel, from port 110, and the signalchannel, from port 114, use a common central processing unit (CPU) 202,with linked storage/memory 204, a power source 206 for the base and acommunications module 208, from which a male type USB (universal serialbus) connector 209 or other similar connector, extends.

The central processing unit (CPU) 202, is formed of one or moreprocessors, in electronic and data communication with storage/memory204, which stores machine executable instructions for execution by theCPU 202, to perform the processes of the dual channels. The power source206 is a battery or plug-in power source. The communications module 208provides network (e.g., Internet) connectivity and communication to andfrom the base 100, in addition to providing the direct connection, forelectronic and data communication between the base 100 and the smartphone 102.

The imaging channel includes the port 110, which receives a microfluidicchip 112 (FIG. 1 ). The microfluidic chip 112 is made viewable by optics308 (FIG. 3 ), including an optomechanical system 212, and an opticalrelay system 214, and ends in an optical module lens 216, through whichan image is transmitted. The optics 308, for example, theopotomechanical system 212, magnifies the sample and enhances the visualpresentation, including images, to being able to achieve high-resolutionof microns, thereof.

The microfluidic chip 112 operates based on capillary action, totransport the received blood, and stain it, in order to be properlyviewed. An optomechanical system 212 (with a controller 212 a) providesfor scanning the microfluidic chip 112 (the scanning provided bymovement of a stand/drawer 302 on a scanning mechanism 304 (FIG. 3 ) bythe controller 212 a) for microscopic viewing, by an optical relaysystem 214, which terminates in an optical module lens 216. There isalso a light (LT) 217 as part of the optomechanical system 212, whichmay be controlled manually (via a switch, button or the like (notshown)) or the controller 212 a. The optomechanical system 212 andoptical relay system 214 are in electronic and/or data communicationeither directly or indirectly with the CPU 202, storage/memory 204,power source 206, and the communications module 208.

FIGS. 6A-6D show various microfluidic chips 112 a-112 d, respectively.

The microfluidic chip 112 a shown in FIG. 6A includes a substrate 601,of glass or polymer or both or other material with/without hydrophiliccoating, suitable for supporting blood and other fluids such as urineand other components, e.g., stain, for microscopy. On the substrate 601is a blood inlet 602, and a stain, encased in a blister (packet) 604, atone end of the substrate 601 a. When use is desired, pressure on theblister 604 ruptures the blister 604 from the tunnel side and press thestain through the microfluidic tunnel 606. The blood and/or a dilutedblood and stain travel via a microfluidic channel 606 to a serpentineshaped microfluidic channel 608 which serves as a mixing region 610 forthe blood and stain. The combines blood and stain, both still moving,travel through another microfluidic channel 612 to a viewing chamber614, at an opposite end 601 b of the substrate. The viewing region 614is configures on the substrate 601 to align with the optics 308 of theoptomechanical system 212 of the apparatus 100, 500.

The microfluidic chip 112 b shown in FIG. 6B includes a substrate 601,for supporting blood and other components, e.g., stain, washingsolution, for microscopy. On the substrate 601 is a blood inlet 622, astain, encased in a blister (packet) 624, and a washing solution,encased in a blister (packet) 626, at one end of the substrate 601 a.When use is desired, blood from the blood inlet 622 flows through themicrofluidic channel 628, leaving blood cells adhered to the walls ofthe microfluidic channel 628. Pressure on the blister 624 ruptures theblister 624, causing the stain to flow through the microfluidic channel628 over the adhered blood cells, such that stain and cells reach thestaining and viewing region 630 on the substrate 601. The staining andviewing region 630 is configured on the substrate 601 to align with theoptics 308 of the optomechanical system 212 of the apparatus 100, 500.Next, pressure on the blister 626 ruptures the blister 626, causing thewashing solution to flow through the microfluidic channel 628 removingany residual stain and dilute the blood-stain mixture.

The microfluidic chip 112 c shown in FIG. 6C includes a substrate 601for supporting blood and other components, e.g., stain, for microscopy.On the substrate 601 is a blood inlet 642 (at one end 601 a of thesubstrate 601), which is at the end of a microfluidic channel 644, whichends in a staining and viewing chamber 646 (at the other end 601 b ofthe substrate 601). The staining and viewing chamber 646 is configuredon the substrate 601 to align with the optics 308 of the optomechanicalsystem 212 of the apparatus 100, 500. Stain, in a dry state, iscontained in the walls of the microfluidic channel 644, such that asblood or a diluted blood 647 flows through the microfluidic channel 644to the staining and viewing region, the blood 647 picks up stain. Thismicrofluidic chip 112 is typically used for viewing single red bloodcells. Here, the microfluidic channel is shallow, approximately 10micrometers in diameter, since the blood is not being diluted.

The microfluidic chip 112 d shown in FIG. 6D includes a substrate 601,for supporting blood and other components. The substrate 601, at one end601 a supports a sample inlet 652, which joins a microfluidic channel654, which, in turn, joins and terminates at a viewing chamber 656, atthe other end 601 b of the substrate 601. A blood sample, diluted ornon-diluted mixed with a stain 657 is placed into the sample inlet 652,where the stained sample flows to the viewing chamber 656. The viewingchamber 656 is configured on the substrate 601 to align with the optics308 of the optomechanical system 212 of the apparatus 100, 500.

The signal channel originates at the port 114, and includes a bio-sensorstrip reader 222, which reads the electrical response (generatedelectrical current from the electrochemical reaction between the sampleand the electrode 116 b, output from the electrode 116 b/biosensor strip116 as an analog signal) from the disposable biosensor electrode 116 b(e.g., at the operative end 116 a of the biosensor strip 116), andamplifies the analog signal of the electrical response, the analogsignal indicative of the electrochemical reaction, for a disease,condition, measurement, or the like. There is an analog to digitalconverter (ADC) 224 which converts the analog signals from the reader222 to digital signals, a signal analysis software module 226, whichanalyzes the digital signals to decide whether or not there is a G6PDdeficiency in this sample, and which communicates with thecommunications module 208, to send the signals to the smart phone 102,for additional analysis.

Alternately, the signal channel can be used for blood glucose leveldetection. The biosensor strip reader 222 is additionally configured toamplify the analog signal(s), generated from the electrical response,from the disposable biosensor electrode (e.g., biosensor strip 116). Theanalog signals correspond to blood glucose levels. The analog to digitalconverter (ADC) 224 converts the analog signals from the reader 222 todigital signals, and a signal analysis module 226, analyzes the digitalsignals received from the ADC 224, to determine the blood glucose levelin the blood sample. This blood glucose level is output in accordancewith standard measurements for blood glucose, to the communicationsmodule 208, to send the signals to the smart phone 102, for additionalanalysis, and for presentation on the display screen (of the smart phone102 or stand-alone device 500, 500′ (FIGS. 5A and 5B)).

Alternately, biosensor strips 116 may include multiple biosensorelectrodes 116 b, including electrodes for producing electricalresponses, convertible into signals readable for detecting G6PDdeficiency and blood glucose levels contemporaneously, and for example,simultaneously.

In other alternatives, the signal channel is usable for otherconditions, such as other diseases, pathogens or biomarkers. Thebiosensor strip reader 222 is additionally configured to amplify orotherwise modify the analog signals produces by the electrical response(electrochemical response) from the electrode on the disposablebiosensor strip. The electrode on the biosensor strip is configured tocreate an electrochemical reaction when contacted by a sample with thecondition, the electrochemical reaction creating a current andcorresponding analog signal for the condition (the biosensor stripreader is configured to recognize the electrochemical signature (orelectrochemical response) of these conditions, and amplify the resultantanalog signal caused by the electrochemical response). The analog todigital converter (ADC) 224 converts the analog signals from the reader222 to digital signals, and a signal analysis module 226 (programmed todetermine the condition, e.g., presence of absence thereof), analyzesthe digital signals received from the ADC 224, to determine thecondition. This condition determination is output, to the communicationsmodule 208, to send the signals of this determination to the smart phone102, for presentation on the display screen (of the smart phone 102 orstand-alone device 500, 500′ (FIGS. 5A and 5B)).

The device, for example, the smart phone 102 includes portions of boththe microscopy channel and the signal channel. The smart phone 102includes a common central processing unit (CPU) 242, with linkedstorage/memory 244, a screen display module 246, which includes logicfor controlling the screen display 103 of the smart phone 102, a GlobalPositioning System (GPS) module 248, data storage 250, such as RAM(Random Access Memory), sensor 252, such as gyrometer, temperature,magnetometer and accelerometer, forming the internal measurement unit(IMU), and a communications module 254, including a female type USB(universal serial bus) connector 255 or other similar connector, forreceiving the male connector 209 in electronic and/or datacommunication. The GPS or location module 248 functions to provide thedisplay of a real-time location indications, based on the incorporatedGPS unit (of the smart phone 102 or as part of the standalone device GPSor location module 548) by mapping of the disease to be used forreal-time mapping and epidemiologic control and learning of the diseasessuch as malaria.

There is also a camera/image sensor unit 260, for converting the cameraimage to signals for display on the screen display 103 (via the screendisplay module 246), an analytics module 264, for image analysis todetect, for example, the type of malaria parasite (e.g. Plasmodium.falciparum, P. vivax, P. malaria. P. ovale, P. Knowlesi and the diseasestage) and perform tagging of the data associated with the particularblood sample. Alternately, the analytics module 264 can be programmed toanalyze and detect other diseases and conditions including, completeblood counts, multi-parasite (e.g. relapsing fever, Filarias),Tuberculosis sputum microscopy, Urine analysis, Pap smear analysis, andthe like, and also veterinary diseases and conditions.

Both the base 100 and smart phone 102 link, via the network(s) 200 to acloud server 270, where each frame sample of malaria parasite, istransmitted to (either directly or from the data storage 250), in orderto update the machine learning of the analytics module 264,cumulatively. With each new image frame sample, the cloud server 270sends the updated machine learning to the analytics module 264, in orderthat it can better detect the malaria parasites. This is done on-line oroff-line whenever a connection is available, automatically orby-request. The cloud server 270 also, for example, stores each testrecord taken, the time, location, diagnosis (both of the parasite andG6PD) patient information and symptoms and more by both the machine 102and optionally, the diagnosis from a telemedicine provider 280, screendisplay, and other information, and can map the malaria cases inreal-time. All data storage and data transmissions over the networks(s)200 between any of the base 100, smart phone 102, cloud server 270,telemedicine provider computers 280 a, 280 b are in accordance withHIPAA (Health Insurance Portability and Accountability Act).

The base 100 and smart phone 102 also link, via the network(s) 200 to atelemedicine provider 280, via a computer 280 a or a smart phone 280 b(via a cellular tower 282), for example. The telemedicine provider 280can provide a diagnosis, that is sent either to the cloud server 270 orback to the analytics module 246 of the smart phone 102.

FIG. 3 shows schematics of the imaging channel and the signal channel.These channels are in portions in both the base 100 and the smart phone102.

The microscopy channel originates at the port 110, which receives themicrofluidic chip 112. This chip 112 uses capillary action to distributethe blood sample and properly stain it and separate the blood cells. Theoptomechanical system 212 includes a stand or a drawer 302 which holdsthe microfluidic chip 112. The stand/drawer 302 is on a scanningmechanism 304 controlled by the controller 212 a, which allows the chip112 to be manipulated to various positions (represented by the doubleheaded oval arrow 306) as per for viewing by the optics 308 of theoptical relay system 214, which terminates in a lens 216 or the like.The screening mechanism (formed by the stand/drawer 302 and scanningmechanism 304) is, for example, based on the drawer 302 movement or theoptically screened, based on the optical design, e.g., using mirror orprisms (which are part of the optical relay system 214).

The image from the optics 308 (including a light 309 (similar to thelight 217 detailed above)) of the optical relay system 214 istransmitted to the lens 320 of the camera 260 of the smart phone 102 orto the stand alone image sensor in case of a stand-alone device. Theimage from the camera 260 is converted to signals by the image sensorunit 262, with the output signals being input into the analytics module264. The output signals also go from the analytics module 264 to thescreen display module 246, so that the blood sample is displayed on thedisplay screen 103.

The analytics module 264, trained by processes including image analysis,machine learning and artificial intelligence (AI), to determine thedisease or condition and provide a diagnosis and/or treatment protocolfor the detected disease or condition. Also, the CPU 202 serves toprovide a diagnosis and/or treatment protocol for the detected diseaseor condition. This detection and/or diagnosis of the disease and/orcondition is, for example, based on morphological “biomarker” analysisof the parasites in their different stages and type. The algorithm(executed by the controller 212 a includes image processing capabilities(in software and/or hardware), segmentation capabilities (in softwareand/or hardware), filters and specific morphological comparison to knownand collected data from the RevDx system The resultant diagnosis data isstored in the data storage 250 and/or in the cloud server 270. Forexample, it is also be transmitted to the telemedicine provider 280 forconfirmation.

The signal channel originates at the port 114. A blood sample on abiosensor strip 116 is placed into the port 114 and the electricalresponse (electrochemical response), derived from the electrochemicalreaction, which produces correlated analog signals. The analog signalsare read by the biosensor reader 222, which amplifies the correlatedanalog signal. The biosensor reader 222 amplifies and, in some casesfilters, the analog signal, which is converted to a digital signal bythe analog to digital converter (ADC) 224. The ADC 224 output of thedigital signal(s) is input into the signal analysis module 226, whichanalyzes the digital signal input, for G6PD deficiency, for example. Adata corresponding to the presence of G6PD from the sample is sent bythe signal analysis module 226 to the communications module 208 and thento the communications module 254 of the smart phone 112. Now in thesmart phone 112, the data is sent from the communications module 254 tothe analytics module 264, where it is analyzed for recommended medicinebased on known treatment procedures. The analytics module 264 signalsthe screen display module 246 to display on the display screen 103, agraphic listing whether there is a G6PD deficiency and the type ofmalaria parasite, what species, its density, stage and other factors.

Alternately, should the signal channel be constructed to provide bloodglucose readings, as detailed above, such blood glucose readings may beobtained with the G6PD output, or separately therefrom, depending on theelectrode(s) 116 b on the biosensor strip 116. For example, the G6PDresult, coupled with a glucose level is analyzed by the CPU 202 todetermine a treatment protocol, for example, as shown in FIG. 7 . Thetreatment protocols, as well as the presence of a disease or conditionis displayed on display screens, smart phone 103, or stand-alone device500, 500′ as a user interface (UI), as directed by the CPU 202 in thedisclosed devices 100, 500, 500′.

The ultimate decision as to the malaria treatment protocol, shouldmalaria be detected, is based on an analysis from both the microscopychannel and the signal channel. This analysis is performed,automatically by the algorithm (run for example by the CPU 202) on-sitein few minutes or in case of uncertainty, the data can be sent on theinternet and analyzed, remotely by a telemedicine provider 280, vianetworks 200.

Similarly, should the signal channel be configured to provide otherreadings of diseases and conditions from the blood, including G6PDoutput, blood glucose, or from urine tests. One of more of theaforementioned are analyzed together, as programmed into the CPU 202, todetermine a treatment protocol.

Attention is now directed to FIGS. 4A and 4B, which show flow diagramsdetailing computer-implemented processes in accordance with embodimentsof the disclosed subject matter. Reference is also made to elementsshown in FIGS. 1-3 . The process and subprocesses of FIGS. 4A and 4B arecomputerized processes performed by the system of the invention, and arefor example, performed manually, automatically, or a combinationthereof, and, for example, in real time.

FIG. 4A is a flow diagram of an example, microscopy process for themicroscopy channel of the invention. Initially a blood sample isobtained and placed onto a microfluidic chip, such as microfluidic chip112, detailed above, and the blood is stained, with the microfluidicchip 112 placed into the base 100, via the port 110, at block 402. Viaan optical relay system (optical relay) 214, at block 404, themicroscopic image of the blood sample, as stained in the microfluidicchip, reaches the camera 260 of the smart phone or in a standalonedevice concept 102. The image in the camera/image sensor unit 260 isconverted to digital data, e.g., digital signals, at block 406. Thedigital data is analyzed, at block 408, by the software analysis module264, by using machine learning and artificial intelligence (AI). Theanalysis module 264 reports a diagnosis, at block 420. Also, at block420, the image of the blood sample is displayed on the screen display103, via screen display module 246. From block 408, the process can moveto block 470, where it ends.

Moving to block 430, from block 420, the data for the blood sample,including the visual image can optionally be tagged, by the analyticsmodule 264.

From block 430, the process can move one or more of three optionalpathways, defined by block in series 440, series 450 and series 460.

Moving from block 430 to block 440, the tagged sample data can bestored, for example, in the data storage 250. The tagged data can thenbe sent from the storage, to a cloud server, such as cloud server 270,at block 442, or directly to the cloud server 270, from block 430 toblock 442. At block 442, in the cloud server 470, updates its machinelearning, artificial intelligence (AI) with the data and diagnosis forthe image. The process moves to block 444, where the analytics module264 is updated with this new data. The process then moves to block 470,where it ends.

Moving from block 430 to block 450, the tagged sample data, or storedtagged sample data (from block 440), in an optional process, can besent, e.g., transmitted over the network(s) 200 to a telemedicinespecialist 280, for example, to his computer 280 a or smart phone,tablet computer, laptop computer 280 b, and the like. At block 452, adiagnosis is received from the telemedicine provider 280, for example,at the smart phone 102, from where the process moves to block 470 whereit ends, or in the cloud server 270. Once in received in the cloudserver 270, the process then moves to block 444, where the analyticsmodule 264 is updated with this new data, or to block 460, detailedbelow. From block 444, the process moves to block 470, where it ends.

At block 460, reached either from block 430, or block 452, the sample,based on a GPS tag and time stamp can be optionally mapped, for example,by the cloud server 270. The process can move to the optional process ofblock 462, where the cloud server 270 provides a map of all the testresults. The process then moves to block 470, where it ends. The processcan also move from block 460 to block 470, where it ends.

FIG. 4B is a flow diagram of an example signal processing process forthe signal channel of the invention. Initially, at block 412, a bloodsample is obtained and placed onto a biosensor strip, such as biosensorstrip 116, detailed above. The biosensor strip 116 is placed into thebase 100, via the port 114, at block 402. The blood sample causes anelectrochemical reaction, which, results in an electrical response beingoutput, at block 414, as an analog signal(s), which is read by thebiosensor reader 222. This analog signal output, for example, asamplified by the biosensor reader 222, is input into an analog todigital converter (ADC) 224, at block 416, which converts the analogsignals to digital signals. The digital signals are then input into asignal analysis module 226, where the signals are analyzed, at block418. The signals then pass to the analysis module 264, which reports adiagnosis, at block 420′. Also, at block 420′ a graphic and absolutenumber indicating the state of the G6PD deficiency is displayed on thescreen display 103, via screen display module 246. From block 418, theprocess can move to block 470, where it ends.

From block 420′ the process can move to the optional processes of block430, 440, 442, 444, 450, 452, 460, 462 and ultimately ending at block470, as detailed above.

FIGS. 5A and 5B shows alternative mobile computing devices 500, 500′ forperforming the disclosed processes via a microscopy channel and a signalchannel. The devices 500, 500′ include components identical or similarto those in device 100, and have the same element numbers, and are inaccordance with that described above for the device 100 of FIG. 2 .Components, including the screen display module 546 (which controls thescreen display 503, e.g., a touch screen, of the device 500), locationbased GPS module 548, data storage 550, sensors IMU 552, image sensorunit 562 and analytics module 564, are identical or similar to thecorresponding components on the smart phone 102 of FIG. 2 , but haveelement numbers in the 500's (rather than the 200's in FIG. 2 ), and arein accordance with the correspondingly numbered component in FIG. 2 .The analytics module 564 analyzes the scanned sample, for example, byimage identification, Artificial Intelligence and the like, to determinethe existence or nonexistence of a disease and/or condition (e.g.,diagnosis of malaria parasites), or a measurement (for example, bloodglucose levels and complete blood cell counts). The optical relay system214 is optional, as the device 500 (FIG. 5A) can work as a standalonedevice, where the lens 216 and the optical relay system 214 are notneeded, or with a smart phone or other device, where the optical relaysystem 214 and lens 216 may be needed. The device 500′ (FIG. 5B) lacksthe optical relay system 214 and the lens 216, and as such, operatesexclusively as a standalone device.

FIG. 5C shows the device 500′ as a stand-alone unit, including a screendisplay 503, which is presenting a screen shot 580. This device 500′ ishand held and therefore portable and battery operated as well as optionfor recharging from external power supply and solar energy.

FIG. 7 shows a process as a decision diagram, for example, programmedinto (and performed by) the CPU 202 of devices 100, 500, and 500′ fortreatment decision support (e.g., providing treatment recommendations,treatment protocols and the like). The treatment recommendations andprotocols appear for example, as user interfaces (UI) on screendisplays, such as those on the screen display 503 of the stand-alonedevice 500′, shown as screen displays (screen shots) 580 a-580 d inFIGS. 8A-8D, and detailed below.

In a first branch of the process, if Falciparum malaria is detected, atblock 702. A glucose check is performed to see if the subject ishypoglycemic, at block 704. If yes, a treatment with artemisinincombination therapy (ACT) is suggested, at block 706. At block 708, ifprimaquine is used for prevention of a further transmission, G6PDdeficiency testing, via devices 100, 500, 500′ disclosed herein, may beused before treatment.

In a second branch of the process, if Non-Falciparum malaria or mixedinfection is detected, at block 712. Treatment is suggested with ACT orchloroquine as well as G6PD testing via devices disclosed 100, 500, 500′herein, at block 714. If G6PD is negative, treatment with primaquine issuggested, at block 716.

In a third branch of the process, should there be a negative test forFalciparum and Non-Falciparum malaria, testing with the devices 100,500, 500′ as disclosed above, is suggested to be performed if thepatient has high clinical suspicion, at block 722.

FIG. 8A shows the device 500′ with a screen shot 580 a showing theresult of a malaria test, and suggesting a treatment protocol. FIG. 8Bshows the device 500′ with a screen shot 580 b showing the result of amalaria test, and providing information on medicines, which could befrom the CPU 202 or a cloud server 270. FIG. 8C shows the device 500′with a screen shot 580 c detailing a white blood cell count. FIG. 8Dshows the device 500′ with a screen shot 580 d detailing a red bloodcell count.

While the devices and methods disclosed above relate to diseases, suchas malaria, these devices are also adaptable for diagnosing otherdiseases conditions and blood count such as white/red blood cell countsand white blood cell differentiation, with various modules programmed torecognize white/red blood cells and for analytics thereof.

The implementation of the method and/or system of embodiments of theinvention can involve performing or completing selected tasks manually,automatically, or a combination thereof. Moreover, according to actualinstrumentation and equipment of embodiments of the method and/or systemof the invention, several selected tasks could be implemented byhardware, by software or by firmware or by a combination thereof usingan operating system.

For example, hardware for performing selected tasks according toembodiments of the invention could be implemented as a chip or acircuit. As software, selected tasks according to embodiments of theinvention could be implemented as a plurality of software instructionsbeing executed by a computer using any suitable operating system. In anexemplary embodiment of the invention, one or more tasks according toexemplary embodiments of method and/or system as described herein areperformed by a data processor, such as a computing platform forexecuting a plurality of instructions. Optionally, the data processorincludes a volatile memory for storing instructions and/or data and/or anon-volatile storage, for example, non-transitory storage media such asa magnetic hard-disk and/or removable media, for storing instructionsand/or data. Optionally, a network connection is provided as well. Adisplay and/or a user input device such as a keyboard or mouse orprinter are optionally provided as well.

For example, any combination of one or more non-transitory computerreadable (storage) medium(s) may be utilized in accordance with theabove-listed embodiments of the present invention. The non-transitorycomputer readable (storage) medium may be a computer readable signalmedium or a computer readable storage medium. A computer readablestorage medium may be, for example, but not limited to, an electronic,magnetic, optical, electromagnetic, infrared, or semiconductor system,apparatus, or device, or any suitable combination of the foregoing. Morespecific examples (a non-exhaustive list) of the computer readablestorage medium would include the following: an electrical connectionhaving one or more wires, a portable computer diskette, a hard disk, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,a portable compact disc read-only memory (CD-ROM), an optical storagedevice, a magnetic storage device, or any suitable combination of theforegoing. In the context of this document, a computer readable storagemedium may be any tangible medium that can contain, or store a programfor use by or in connection with an instruction execution system,apparatus, or device.

A computer readable signal medium may include a propagated data signalwith computer readable program code embodied therein, for example, inbaseband or as part of a carrier wave. Such a propagated signal may takeany of a variety of forms, including, but not limited to,electro-magnetic, optical, or any suitable combination thereof. Acomputer readable signal medium may be any computer readable medium thatis not a computer readable storage medium and that can communicate,propagate, or transport a program for use by or in connection with aninstruction execution system, apparatus, or device.

As will be understood with reference to the paragraphs and thereferenced drawings, provided above, various embodiments ofcomputer-implemented methods are provided herein, some of which can beperformed by various embodiments of apparatuses and systems describedherein and some of which can be performed according to instructionsstored in non-transitory computer-readable storage media describedherein. Still, some embodiments of computer-implemented methods providedherein can be performed by other apparatuses or systems and can beperformed according to instructions stored in computer-readable storagemedia other than that described herein, as will become apparent to thosehaving skill in the art with reference to the embodiments describedherein. Any reference to systems and computer-readable storage mediawith respect to the following computer-implemented methods is providedfor explanatory purposes, and is not intended to limit any of suchsystems and any of such non-transitory computer-readable storage mediawith regard to embodiments of computer-implemented methods describedabove. Likewise, any reference to the following computer-implementedmethods with respect to systems and computer-readable storage media isprovided for explanatory purposes, and is not intended to limit any ofsuch computer-implemented methods disclosed herein.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

The descriptions of the various embodiments of the present inventionhave been presented for purposes of illustration, but are not intendedto be exhaustive or limited to the embodiments disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the describedembodiments. The terminology used herein was chosen to best explain theprinciples of the embodiments, the practical application or technicalimprovement over technologies found in the marketplace, or to enableothers of ordinary skill in the art to understand the embodimentsdisclosed herein.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

The above-described processes including portions thereof can beperformed by software, hardware and combinations thereof. Theseprocesses and portions thereof can be performed by computers,computer-type devices, workstations, processors, micro-processors, otherelectronic searching tools and memory and other non-transitorystorage-type devices associated therewith. The processes and portionsthereof can also be embodied in programmable non-transitory storagemedia, for example, compact discs (CDs) or other discs includingmagnetic, optical, etc., readable by a machine or the like, or othercomputer usable storage media, including magnetic, optical, orsemiconductor storage, or other source of electronic signals.

The processes (methods) and systems, including components thereof,herein have been described with exemplary reference to specific hardwareand software. The processes (methods) have been described as exemplary,whereby specific steps and their order can be omitted and/or changed bypersons of ordinary skill in the art to reduce these embodiments topractice without undue experimentation. The processes (methods) andsystems have been described in a manner sufficient to enable persons ofordinary skill in the art to readily adapt other hardware and softwareas may be needed to reduce any of the embodiments to practice withoutundue experimentation and using conventional techniques.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

The invention claimed is:
 1. A dual channel diagnostic devicecomprising: an imaging channel comprising: a first port for providingthe diagnostic device with a first sample; an optical system forrendering the first sample as an image viewable on a display; an imagerfor obtaining an image of the first sample from the optical system; andan analytics module configured for analyzing the image of the firstsample and providing a diagnosis including a determination of one of: afirst disease condition or test result, from the image; and, a signalchannel comprising: a second port for providing the diagnostic devicewith a second sample; a signal generator in communication with anelectrochemical sensor for converting an electrochemical response fromthe electrochemical sensor from an electrode having reacted with thesecond sample; and a signal analyzer for analyzing received signals fromthe signal generator, to providee a diagnosis including thedetermination of one of: a second disease condition or test result;wherein a disease condition or test result is determined from one orboth of the first disease condition or test result and the seconddisease condition or test result.
 2. The device of claim 1, wherein theanalytics module is configured for the providing of the diagnosis, fromthe image, 1) for a disease condition including: anemia, malariaparasites including, P. falciparum, P. vivax, P. malaria. P. ovale, P.knowlesi and the disease stage, multi-parasites including relapsingfever and Filarias, Tuberculosis, and, veterinary diseases, and 2) for atest result including: blood count, malaria parasites including, P.falciparum, P. vivax, P. malaria. P. ovale, P. knowlesi, complete bloodcell counts, Pap smear analysis, multi-parasites, and urine tests. 3.The device of claim 1, wherein the microscopy system includes anoptomechanical system for magnifying the first sample.
 4. The device ofclaim 1, additionally comprising: a processor programmed to determine atreatment for the provided diagnosed disease condition or the testresult, the processor in communication with the analytics module.
 5. Thedevice of claim 1, additionally comprising: a processor programmed todetermine a treatment for the provided diagnosed disease condition orthe test result, the processor in communication with the analyticsmodule and the signal analyzer.
 6. The device of claim 1, wherein theimaging channel and the signal channel are configured to output theprovided diagnosed disease condition or the test result in real time. 7.The device of claim 1, additionally comprising: a display incommunication with the imaging channel and the signal channel, thedisplay comprising: 1) a screen display, and/or, 2) a display outputconfigured for communicating with an image sensor of an externalcomputer device for displaying graphics on the display screen of theexternal computer device.
 8. The device of claim 7, wherein the imagingchannel includes a first end including the first port, and an oppositelydisposed second end associated with the display.
 9. The device of claim7, additionally comprising a processor programmed to transmit data tothe display which causes presentation of a User Interface (UI) graphicdisplay of the presence of the diagnosed disease condition.
 10. Thedevice of claim 1, additionally comprising: an analog to digital signalconverter (ADC) in communication with the signal analyzer; and, a signalreader in communication with the electrochemical sensor for readingelectrochemical signals emitted from the electrode having reacted withthe second sample, the signal reader in communication with the ADC. 11.The device of claim 10, wherein the signal analyzer is configured foranalyzing signals to provide the diagnosed disease condition or the testresult selected from the group comprising: G6PD output, and bloodglucose levels, malaria parasites including, P. falciparum, P. vivax, P.malaria. P. ovale, P. knowlesi and the disease stage, complete bloodcell counts, multi-parasites including: relapsing fever and Filarias,Tuberculosis, Pap smear analysis, and veterinary diseases.
 12. Thedevice of claim 1, additionally comprising: a location module incommunication with at least one of the imaging channel or the signalchannel, the location module configured for displaying real- timelocation indications based on Global Positioning System (GPS) mapping ofthe diagnosed disease condition or the test result.
 13. The device ofclaim 1, additionally comprising: a microfluidic chip for holding thefirst sample, the microfluidic chip n for receipt in the first port. 14.The device of claim 13, wherein the microfluidic chip is configured formixing the first sample with one or more staining agents, imagingenhancers, and dilutants.
 15. The device of claim 1, additionallycomprising: a biosensor strip including an electrode for producing anelectrochemical response when contacted by the second sample, forreceipt in the second port.
 16. The device of claim 1, where the firstdisease condition or test result and the second disease or test resultare the same disease condition or test result.
 17. The device of claim1, where the first disease condition or test result and the seconddisease or test result are a different disease condition or test result.18. The device of claim 1, wherein the imager comprises at least one of:a camera, a scanner, and one or more image sensors.
 19. The device ofclaim 1, wherein the first sample and the second sample are from a samesource comprising at least one of: tissue, blood, urine, sputum, andbodily fluid.
 20. A method for analyzing tissue samples comprising:providing a first sample to an imaging channel of a dual channeldiagnostic device via a first port; with the first sample in the imagingchannel: rendering the first sample as an image viewable on a display;obtaining an image of the first sample; analyzing the image of the firstsample, and, providing a diagnosis including a determination of one of:a first disease condition or test result, from the image; providing asecond sample to a signal channel of the dual channel diagnostic device;and with the second sample in the signal channel: generating signalscorresponding to an electrochemical response received by anelectrochemical sensor from an electrode having reacted with the secondsample; analyzing the generated signals to provide a diagnosis includingthe determination of one of: a second disease condition or test result;and determining a diagnosis comprising a disease condition or testresult from one or both of the first disease condition or test resultand the second disease condition or test result.
 21. The method of claim20, wherein information as to the determined diagnosis is outputted tothe display.
 22. The method of claim 20, wherein the first sample andthe second sample include portions of the same sample which comprises atleast one of blood, urine, and tissue.
 23. The method of claim 20,wherein the first disease condition or test result and the seconddisease condition or test result are either: 1) the same diseasecondition or test result, or 2) a different disease condition or testresult.